Flexible manufacture of polymeric tubing

ABSTRACT

Tubular polymeric structures are formed by creating a convex mold conforming to a fluid pathway design, depositing a coating of polymer over the mold, and in situ removing the mold without drawing it against the polymer.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to and the benefit of, and incorporatesherein by reference in its entirety, U.S. Ser. No. 61/821,039, filed onMay 8, 2013, the entire disclosure of which is hereby incorporated byreference.

TECHNICAL FIELD

The present invention relates to microfluidic channels and methods fortheir manufacture, and more particularly to conduits capable ofaccommodating fluid paths with tight radii and varying cross-sections.

BACKGROUND

The need for ever-smaller pumping devices, particularly in the medicalfield, continues to grow. As a result, the need for increasingly smalloperational pump components is growing as well, challenging the limitsof conventional manufacturing processes. As fluidic devices shrink, itis necessary to manufacture fluidic paths with very tight radii andvarying cross-sections to fit within the device package. Some of thesecross-sections may not be round, and it may be necessary to form fluidicconnectors directly into the fluid paths themselves.

Conventional manufacturing techniques have various limitations. Oneapproach to creating polymeric fluidic paths is to use photoresist tocreate a channel in a layered polymer. Once the polymer has been layeredover the photoresist, it is dissolved to leave a fluid channel; see,e.g., Jason Shih, 2008 “Microfabricated High-Performance LiquidChromatography (HPLC) System With Closed-Loop Flow Control,” Ph.D.thesis, Department of Mechanical Engineering, California Institute ofTechnology. Another approach is to use polymer extrusion to create smallfluid channels; see, e.g., Lopez, Fernando L., 2011, “Micro-SizedComponents for Medical Extrusion,” Interface Catheter Solutions,California, USA. This is a standard method of fabrication for cathetersand other macro-scale tubes. Although varying interior diameters andwall thicknesses are achieved by manipulating extrusion speed and dieconfigurations, shapes such as tight-radius twists and bends are noteasily replicable. A third approach is three-dimensional (3D) waxprinting to create other types of structures for use in devices. Thisapproach has been used to create relatively large 3D structures coatedwith very thin polymer layers; see, e.g., Feng, Guo-Hua and Kim, EunSuk, 2003, “Universal Concept for Fabricating Micron to Millimeter Sized3D Parylene Structures on Rigid and Flexible Substrates,” The SixteenthAnnual International Conference on Micro Electro Mechanical Systems,2003, pp. 594-597.

Unfortunately, conventional approaches such as these do not readilyallow for the creation of fluid paths of a tortuous nature, havingvarying radii and minute dimensions, and with a smooth finish asnecessary for long-term use, especially in implantable drug pumps.Smooth fluid paths within an implantable drug pump are generallynecessary to avoid or minimize structures that promote drug aggregation,to reduce clogging, and to avoid long-term biofouling.

SUMMARY

Manufacturing techniques in accordance herewith are capable of creatinga wide array of fluidic paths that meet demanding design criteria.Although the following discussion focuses on parylene(poly(p-xylylene)), it should be understood that the invention isapplicable to many polymer systems, particularly those applied by vapordeposition, as will be apparent to those skilled in the art.

In one aspect, the invention pertains to a method of forming a tubularpolymeric structure. In various embodiments, the method comprises thesteps of forming a convex mold conforming to a fluid pathway design, themold being formed of a material soluble in a solvent; depositing acoating of polymer over the mold to form a coated structure, theparylene being unaffected by exposure to the solvent; and in situremoving the mold by subjecting the coated structure to the solvent. Insome embodiments, the material comprises or consists essentially of wax,whereas in other embodiments, the material comprises or consistessentially of a thermoplastic. The polymer may, for example, beparylene. The method may further include trimming one or more ends ofthe tubular polymeric structure to expose a lumen thereof.

In various embodiments, the mold is formed by 3D printing. For example,the mold may be formed into a block of support wax, in which case themethod may further comprise dissolving the support wax but not the waxmold. In general, following deposition of the polymer, the mold isdissolved with a solvent that does not dissolve the polymer.

In various embodiments, prior to deposition of the polymer, the moldsundergo a smoothing process. The smoothing process may, for example,comprise or consist essentially of passing a solvent vapor over themold. Alternatively, the smoothing process may comprise or consistessentially of spin coating and baking photoresist over the mold. Instill another alternative, the smoothing process may comprise or consistessentially of spray coating polyvinyl alcohol over the mold.

In alternative embodiments, the method comprises the steps of forming aconvex mold conforming to a fluid pathway design; depositing a polymercoating over the mold to form a coated structure; and in situ removingthe mold by heating the coated structure to a temperature sufficient tomelt the mold but which does not damage the polymer. In someembodiments, the material comprises or consists essentially of wax,whereas in other embodiments, the material comprises or consistessentially of a thermoplastic. The polymer may, for example, beparylene. The mold may be formed by 3D printing.

In another aspect, the invention relates to a method of forming aparylene manifold structure. In various embodiments, the methodcomprises the steps of forming a mold having a cavity and, therein, ascaffold complementary to one or more fluid paths, the mold and thescaffold being formed of a material soluble in a solvent; filling thecavity with a polymer and causing the polymer to harden, the polymerbeing unaffected by exposure to the solvent; and in situ removing themold including the scaffold by subjecting it to the solvent.

In some embodiments, alignment features are formed in the cavity.Following hardening of the polymer, the mold may be dissolved with asolvent that does not dissolve the polymer; alternatively (or inaddition), following hardening of the polymer, the mold may be melted ata temperature that does not damage the polymer. Once again, the polymermay be parylene, and the method may further include trimming one or moreends of the tubular polymeric structure to expose a lumen thereof.

In yet another aspect, the invention relates to a method of forming atubular polymer structure. In various embodiments, the method comprisesthe steps of bending a wire to conform to a fluid pathway design;depositing a coating of polymer over the wire; and in situ removing thewire without drawing it against the polymer. In some embodiments, thewire is copper and the removing step comprises etching away the wire byexposure of the coated wire to an etchant; for example, the etchant maybe ferrite chloride.

In some embodiments, the wire is made of a metal having a melting pointlower than the melting point of the polymer (which may, for example, beparylene). For example, the wire may be Field's metal. The method mayfurther comprise the step of shaping a cross-section of the wire priorto the depositing step.

As used herein, the term “substantially” or “approximately” means±10%(e.g., by weight or by volume), and in some embodiments, ±5%. The term“consists essentially of” means excluding other materials thatcontribute to function, unless otherwise defined herein. Nonetheless,such other materials may be present, collectively or individually, intrace amounts.

Reference throughout this specification to “one example,” “an example,”“one embodiment,” or “an embodiment” means that a particular feature,structure, or characteristic described in connection with the example isincluded in at least one example of the present technology. Thus, theoccurrences of the phrases “in one example,” “in an example,” “oneembodiment,” or “an embodiment” in various places throughout thisspecification are not necessarily all referring to the same example.Furthermore, the particular features, structures, routines, steps, orcharacteristics may be combined in any suitable manner in one or moreexamples of the technology. The headings provided herein are forconvenience only and are not intended to limit or interpret the scope ormeaning of the claimed technology.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be more readily understood from the followingdetailed description of the invention, in particular, when takenconjunction with the drawings, in which:

FIG. 1A illustrates the results of a layered fabrication process forforming tubes in accordance with one embodiment;

FIG. 1B shows a scaffold for production of multiple similar fluidconduits in a single manufacturing sequence;

FIG. 2 illustrates fabrication of a solid manifold containing a fluidpath in accordance with one embodiment; and

FIG. 3 illustrates fabrication of a branched-tube manifold in accordancewith one embodiment.

DETAILED DESCRIPTION 1. Wire Mandrel Method

In one embodiment, a method of tube manufacture utilizes a metal (e.g.,copper) wire to fabricate fluid paths with very good control of interior(lumen) dimension and excellent surface finish. In a representativeembodiment, the process starts by cutting a length of copper wire havinga diameter equal to that of the intended tube inner diameter (ID). Thelength of the cut copper wire is typically much longer than the lengthof tube being fabricated. If desired, the wire may be shaped using apressing tool such as a jig that has been machined to correspond to thedesired lumen geometry of the tube. For example, a wire with a roundcross-section may be pressed in a jig so that its cross-section is atriangle, square or other polygon. Of course, any suitable machining (orother mechanical) technique may be used to shape the wire, and indeed,wire having a desired cross-sectional shape and diameter may beobtainable commercially. Furthermore, other metals including platinum,tungsten, silver, and various alloys may be used in lieu of copper, butcopper is preferred because the copper and ferrite chloride reactiondoes not generate gases as a byproduct. This makes etching easierwithout an additional process or the need to remove the gas generated byetching, which is inconvenient and may operate to inhibit the etchingprocess.

The wire with the required cross-sectional geometry may be bent into ashape corresponding to the desired fluid routing path. The wire is thenplaced in a parylene deposition chamber and a layer of parylene ofdesired thickness (e.g., 20 μm) is deposited thereon, for example, byvapor deposition. After deposition, the parylene-coated wire is trimmedof polymer at both ends to expose the copper. The trimmed, coated wireis then placed in a solution that will dissolve the wire without harmingthe polymer coating; for example, in the case of a copper wire, aferrite chloride solution can be used, typically requiring up to 3 weeksto fully remove the copper. At the end of the etching process only theparylene tube remains. The parylene tube may then be trimmed to theproper length for use.

This method allows for the creation of tubing with highly accurateinternal dimensions as wire with a specifically engineered cross-sectionand consistent cross-section is used in the process. In addition, sincethe wire may have excellent surface finish, the resulting tube will havevery smooth inner surfaces. Unlike extrusion, this method results in arigid tube that is shaped to conform to the desired fluid path (asopposed to having to shape a straight tube). It may also create a tubewith a round cross-section, which facilitates easy fluidic connections.The copper wire may be pre-machined to different cross-sectional shapesor varying radii to create further intricate structures.

In a variation of this approach, the wire is made of a bismuth, indium,and tin alloy (generally 32.5% Bi, 51% In, and 16.5% Sn) called aField's metal. This soft metal can be shaped arbitrarily, but melts at62° C. Accordingly, instead of using a chemical solution to remove themetal, the parylene-coated wire can be heated to the melting point ofthe metal, which will simply flow out of the tube. Once again, the wiremay be pressed into a jig to give the wire the proper geometry, andfollowing polymer deposition, the wire is clipped at both ends to allowthe metal to flow out in the next step. A fixture may be used foraccurate trimming. The coated wire is placed in an oven set for 62° C.and oriented upright. When the metal reaches 62° C. it melts, leavingonly the polymer outer coating behind. The polymer tube is then trimmedto length for use.

This method creates tubing with a highly accurate internal diameter aswire with known tolerance is used in the process. In addition, since thewire has excellent surface finish, the resulting tube has very smoothinner surfaces. Unlike extrusion, this method results in a rigid tubethat is shaped to the proper routing as opposed to having to affix astraight tube in the proper orientation. It can be used to create a tubewith a round cross-section, which makes fluidic connections very easy tomake. Unlike the copper wire method, the wire removal time is a matterof hours as opposed to weeks.

2. 3D Mandrel Method of Tube Manufacture

A second manufacturing technique uses a material, such as wax, solublein an organic (typically nonpolar) solvent as a 3D printing material tobuild a convex mold or scaffold onto which a controlled-thickness layerof a polymer such as parylene C is deposited; the polymer is unaffectedby the solvent. As used herein, the term “wax” refers broadly to anylipid compound (or mixture of compounds) that is solid at roomtemperature. Typically, the molecular structure of a wax consists of orcomprises long alkyl chains that may or may not have functional groups,and that may include intrachain linkages such as ester linkages Waxesmay be natural or synthetic, and may be a single component or a blend ofcomponents. Furthermore, other materials such as thermoplastics ororganic mixtures may be used as the printing material so long as theyare soluble in a suitable solvent. While the ensuing discussion refersto wax for ease of explanation, it should be understood that thesealternative materials may be used instead.

The geometry and cross-section of the structure may be created bybuilding up layers of wax to create any arbitrary shape. Followingdeposition of the parylene onto the mold, the wax is dissolved, leavingonly the outer layer of deposited parylene. The result is a tube ofcontrolled wall thickness and accurately controlled cross-section andgeometry.

The wax scaffold may be formed in any suitable manner, including,without limitation, molding, extrusion, or selective, layer-by-layerdeposition onto a surface in a manner that builds up a 3D structure—aprocess often termed “3D printing.” This wax-scaffold approach to tubefabrication allows for the manufacture of parylene tubes of arbitrarycross-section and routing with very accurate dimensional control. In arepresentative embodiment, illustrated in FIG. 1A, a 3D wax printer isused to build up the wax scaffold within a block of support wax. Theshape and size of a desired cross-section 100 is defined, and a seriesof flat, elongated wax layers 110 (e.g., having a thickness of 6.35 μm)is sequentially deposited. The layers 110 may follow a tortuous path butalong the dimension of deposition roughly conform, collectively, to thecross-section 100—that is, the layers 110 fit as snugly as possiblewithin the envelope defined by the cross-section 100.

Once printed, the resulting wax tube mold 120 has a rough and steppedappearance from the layered addition of wax material during the printingprocess. This can cause the subsequently deposited polymer to be roughand opaque in appearance. To improve the surface finish, a smoothingprocess is desirably performed on the printed wax molds. One such methodis using a solvent vapor such as acetone to smooth the tube molds. Usinga convective air current to pass a solvent vapor over the molds, the toplayer of wax is softened and reflows over the surface. The resultingmold surface finish is smooth without loss of the material.

The support wax melts at a lower temperature than the deposited wax—forexample, the support wax may be a wax mixture (e.g., a naturallyproduced wax) while the deposited wax may be paraffin. The support blockretains the printed wax parts as they are built up in order to preventthem from breaking apart prior to completion. Once the printing iscomplete, the structure is heated to a temperature sufficient to meltthe support wax but low enough to leave the printed wax unaffected (or,alternatively, the structure is subjected to a solvent that dissolvesthe support wax but not the deposited wax). For example, certain formsof bee's wax melt at 30° C., paraffin may melt at approximately 55° C.,and synthetic waxes may have melting points as high as 75° C. Usingreadily available equipment, 3D printing can be controlled to anaccuracy of 25.4 μm and can fabricate a minimum feature size of 254 μm;suitable 3D printers include the SOLIDSCAPE T76Plus device marketed bySolidscape Inc., Merrimack, N.H. and the ProJet 3500 series of devicesmarketed by 3D Systems, Inc., Rock Hill, S.C. The support block mayitself be printed or may instead be molded in the form of a block with arecess, the bottom surface of which receives the deposited wax.

An alternative smoothing technique for the wax tube molds utilizes amicroelectromechanical system (MEMS) approach. First, a photoresist suchas SU-8 is spin-coated onto the printed wax molds. The solvent in thephotoresist acts to dissolve away any defects while the resist itselfhelps to fill the surface steps in the wax mold. Several iterations ofthe spin coating may be required to achieve the final desired surfacefinish. The resist is then baked on the molds to evaporate the solventand harden the resist. This step creates an even surface finish over theentire mold surface while maintaining the shape and size of the tubemold.

In specific applications, it may be desired to create a slightlysmaller-diameter tube. By increasing the solvent composition,concentration, or spin coating time, the wax tube may be reduced in sizein a controlled fashion by, for example, 5% or 10%. Such an approach canbeneficially reduce the size of the tube to dimensions below thecapability of the wax printer while also smoothing the surface. Forexample, a 200 μm diameter structure may be out of the range of the waxprinter, which produces (for example) a 230 μm structure with a roughsurface of 10 μm. By increasing the photoresist contact duration, thewax mold can be smoothed and reduced to obtain the target 200 μmdiameter structure.

The second step addresses the opacity of the parylene after deposition.After spinning and baking the SU-8 photoresist, a thin layer ofpolyvinyl alcohol (PVA) solution may be sprayed on the photoresistcoated molds. The PVA gives a shine to the molds that causes thedeposited parylene to be transparent. Several coats of PVA solution maybe required to achieve the desired shine on the wax molds.

The smoothing process may also be used for extra dimensional control ofthe wax molds when, once again, the required dimensions or tolerancescannot be created or maintained by the wax printer itself. Allowing theSU-8 photoresist to remain on the surface of the mold before baking fora longer time period will reduce the size of the mold features. Thisfacilitates incorporation of features that are smaller than the minimumsize achievable using available 3D printing technology. Increasing thetime the SU-8 photoresist remains on the mold during spinning from 10 upto 20 seconds decreases the feature size by 10%-15% from the 3D printeddimension. By adjusting this spin time, very accurate dimensionalchanges and control can be achieved.

Once the mold is smoothed, it is placed in a parylene deposition chamberin which a controlled thickness (e.g., 20 μm) of a polymer (e.g.,parylene C) is deposited on the surface. After parylene deposition, theends of the resulting tubular structure are clipped to expose the wax oneach end to the outside environment. A fixture may be used for accuratetrimming. The structure is then placed in acetone or another othersuitable solvent to dissolve away the wax mold from the inside. After24-48 hours of soak time in acetone, only the parylene outer layerremains.

Unlike other tube manufacturing methods, 3D printing as described hereineasily allows for production of tubes of virtually any shape, diameter,and routing. FIG. 1B illustrates how a single scaffold 140 may be usedto create a plurality of tubes in a single batch run without additionalhandling. The molds 150 for the individual tubes may each be anchored tothe scaffold 160 by a mold segment 170 that produces a fludic connector.In use following fabrication, the fluidic connector is used to connectthe tubing segment to a conduit (e.g., another tubing segment). Thefluidic connector may have a specific cross-sectional geometry (e.g.,off-round, polygonal, etc.) to align and connect the tube to an adjacentconduit.

The connector portion typically has a wider diameter than the tube,which serves to sturdy the point of attachment to the scaffold 160, andin some embodiments, the mold segments 170 flare where they are joinedto the scaffold 160 in order to increase the surface area of contactwith the scaffold and provide further sturdiness to the mold, therebyavoiding inadvertent removal of the molds during manufacture. The flaredsegment may or may not be part of the finished tube; that is, it may becut away from the connector or represent a part of it. For example, aconically flared connector portion can provide stress relief when thetube is connected to another conduit.

Following polymer application and cure, the resulting polymer tubes maybe cut away from the scaffold 160, and the distal end of each tube maybe removed to expose the lumen. The tubes may be subjected to the actionof a solvent at this point, but in some embodiments, this occurs whilethe molds 170 are still adhered to the scaffold 160, which resists theaction of the solvent that removes the molds 150 (and so can bere-used). The wax printing method for tube production provides highlyaccurate tubing structures with minimal manual handling andmanufacturing.

3. Solid Manifold Method of Tube Manufacture

The present invention may be used to form a solid manifold with internalfluid paths. A solid manifold is critical for some microfluidicconfigurations (e.g., modular designs assembled from interchangeablefluid-path components), and more generally offer increased tubingstrength, ease of handling, and ease of component integration. Byutilizing the flexibility of wax printing technology, manifolds ofnearly any configuration can be made. A representative fabricationsequence is shown in FIG. 2. First, a wax mold 200 is printed, molded orotherwise fabricated with an internal cavity 210. Within the cavity 210,a wax structure corresponding to the desired tubing configuration(s) 215is printed. Next, the cavity 210 is filled with a liquid form of thematerial that will compose the manifold, e.g., a curable polymericmaterial such as parylene, silicone or epoxy. After the material 215 iscured (e.g., by exposure to actinic radiation or e-beam, or simply byallowing it to dry and harden), the wax is removed from the finishedstructure to create the solid manifold 230 containing internalmicrofluidic passages complementary to the wax structure 215. The waxmay be removed from the manifold 230 by heating it to the melting pointof the wax and allowing to flow out of the manifold (assisted by an airjet if needed), or by subjection to a solvent for the wax. The more themanifold is cross-linked, the greater will be useful range of solvents,since few solvents will harm a fully cross-linked polymer. The originalwax mold 215 may contain additional structural features (pins, slots,indents, partial tubes, grooves, etc.) to help align and connect thetube set with an adjacent component during component integration.

4. Branched Tube Manifold Method of Tube Manufacture

As illustrated in FIG. 3, a branched tube manifold may be created toconsolidate the number of connections as well as reduce the spacerequired for fluidic connections. In a representative fabricationsequence, a wax mold 300 with extensions along multiple fluidic paths ismolded or printed. The surface of the wax mold 300 is preferablysmoothed as described above. Next, the wax mold is coated with a polymersuch as parylene to form a coated structure 310. Finally, the wax moldis heated or dissolved away, leaving parylene tubing 320 conforming tothe fluid path defined by the mold 300.

Various embodiments of the invention are described above. It will,however, be apparent to those of ordinary skill in the art that otherembodiments incorporating the concepts disclosed herein may be usedwithout departing from the spirit and scope of the invention.Accordingly, the above description is intended to be only illustrativeand not restrictive.

What is claimed is:
 1. A method of forming a tubular polymericstructure, the method comprising the steps of: forming a convex moldconforming to a fluid pathway design, the mold being formed of amaterial soluble in a solvent; depositing a coating of polymer over themold to form a coated structure, the parylene being unaffected byexposure to the solvent; and in situ removing the mold by subjecting thecoated structure to the solvent.
 2. The method of claim 1 wherein thematerial is wax.
 3. The method of claim 1 wherein the material is athermoplastic.
 4. The method of claim 1 wherein the polymer is parylene.5. The method of claim 1 wherein the mold is formed by 3D printing. 6.The method of claim 2 wherein the mold is formed into a block of supportwax, and further comprising the step of dissolving the support wax butnot the wax mold.
 7. The method of claim 1 wherein, prior to depositionof the polymer, the molds undergo a smoothing process.
 8. The method ofclaim 7 wherein the smoothing process comprises passing a solvent vaporover the mold.
 9. The method of claim 7 wherein the smoothing processcomprises spin coating and baking photoresist over the mold.
 10. Themethod of claim 7 wherein the smoothing process comprises spray coatingpolyvinyl alcohol over the mold.
 11. The method of claim 1 furthercomprising trimming one or more ends of the tubular polymeric structureto expose a lumen thereof.
 12. A method of forming a tubular polymericstructure, the method comprising the steps of: forming a convex moldconforming to a fluid pathway design; depositing a polymer coating overthe mold to form a coated structure; and in situ removing the mold byheating the coated structure to a temperature sufficient to melt themold but which does not damage the polymer.
 13. The method of claim 12wherein the material is wax.
 14. The method of claim 12 wherein thematerial is a thermoplastic.
 15. The method of claim 12 wherein thepolymer is parylene.
 16. The method of claim 12 wherein the mold isformed by 3D printing.
 17. The method of claim 12 further comprisingtrimming one or more ends of the tubular polymeric structure to expose alumen thereof.
 18. A method of forming a parylene manifold structure,the method comprising the steps of: forming a mold having a cavity and,therein, a scaffold complementary to one or more fluid paths, the moldand the scaffold being formed of a material soluble in a solvent;filling the cavity with a polymer and causing the polymer to harden, thepolymer being unaffected by exposure to the solvent; and in situremoving the mold including the scaffold by subjecting it to thesolvent.
 19. The method of claim 18 wherein alignment features areformed in the cavity.
 20. The method of claim 18 wherein, followinghardening of the polymer, the mold is dissolved with a solvent that doesnot dissolve the polymer.
 21. The method of claim 18 wherein, followinghardening of the polymer, the mold is melted at a temperature that doesnot damage the polymer.
 22. The method of claim 18 wherein the polymeris parylene.
 23. A method of forming a tubular polymer structure, themethod comprising the steps of: bending a wire to conform to a fluidpathway design; depositing a coating of polymer over the wire; and insitu removing the wire without drawing it against the polymer.
 24. Themethod of claim 23 wherein the wire is copper and the removing stepcomprises etching away the wire by exposure of the coated wire to anetchant.
 25. The method of claim 24 wherein the etchant is ferritechloride.
 26. The method of claim 23 wherein the wire is made of a metalhaving a melting point lower than a melting point of the polymer. 27.The method of claim 23 wherein the wire is Field's metal.
 28. The methodof claim 23 wherein the polymer is parylene.
 29. The method of claim 23further comprising the step of shaping a cross-section of the wire priorto the depositing step.